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MEDICINES MANAGEMENT TOOL FOR ANTIPSYCHOTICS
Document Reference
G368
Version Number
3.0
Author/Lead Job Title
Wendy Tucker Jackie Stark
Date last reviewed, (this version) August 2014
Date of Next Review
August 2016
Ratified by: Committee OR Business Unit Head
HFT Drug and Therapeutics Committee
VALIDITY – Documents should be accessed via the Trust internet to ensure the current version is used.
CHANGE RECORD
Version Date Change details
May 2013 Minor updates to relative risks for some medications and inclusion of asenapine. Random plasma glucose removed from monitoring as fasting plasma glucose or HbA1c more appropriate
Aug 2014 Changes in monitoring parameters due to updated information
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Medicines Management Tool for Antipsychotics
BACKGROUND ................................................................................................................... 3
WEIGHT GAIN ..................................................................................................................... 4 Background .............................................................................................................................................. 4 Monitoring of Weight................................................................................................................................. 4 Strategies for Minimisation of Weight Gain .............................................................................................. 5 Management of Weight Gain .................................................................................................................... 6
HYPERPROLACTINAEMIA ................................................................................................. 7 Background .............................................................................................................................................. 7 Monitoring for the Effects of Raised Prolactin .......................................................................................... 7 Strategies for Minimisation of Hyperprolactinaemia ................................................................................. 7 Management of Hyperprolactinaemia ...................................................................................................... 8
SEDATION ........................................................................................................................... 9 Background .............................................................................................................................................. 9 Monitoring for the Effects of Sedation ...................................................................................................... 9 Strategies for Minimisation of Sedation .................................................................................................... 9 Management of Sedation ....................................................................................................................... 10
EXTRAPYRAMIDAL SIDE EFFECTS (EPSE) ................................................................... 11 Background ............................................................................................................................................ 11 Monitoring for EPSE ............................................................................................................................... 11 Strategies for Minimisation of EPSE ...................................................................................................... 12 Drug Treatment of EPSE ........................................................................................................................ 12 Management of EPSE ............................................................................................................................ 13
HYPERLIPIDAEMIA ........................................................................................................... 14 Background ............................................................................................................................................ 14 Monitoring for Hyperlipidaemia ............................................................................................................... 14 Strategies for Minimisation of Hyperlipidaemia ...................................................................................... 16 Management of Hypercholesterolemia................................................................................................... 16
POSTURAL HYPOTENSION ............................................................................................. 18 Background ............................................................................................................................................ 18 Monitoring for Postural Hypotension ...................................................................................................... 18 Strategies for the Minimisation of Postural Hypotension........................................................................ 18 Management of Postural Hypotension ................................................................................................... 19
OTHER CARDIOVASCULAR SIDE EFFECTS ................................................................. 20 Stroke ..................................................................................................................................................... 20 QTc Prolongation.................................................................................................................................... 20 Myocarditis and Cardiomyopathy ........................................................................................................... 20
HYPERGLYCAEMIA .......................................................................................................... 21 Background ............................................................................................................................................ 21 Monitoring for Hyperglycaemia ............................................................................................................... 21 Strategies for the Minimisation of Hyperglycaemia ................................................................................ 21 Management of Hyperglycaemia ............................................................................................................ 22
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Background
Individual antipsychotic drugs differ by the range and extent of their side effect profile, principally in the following areas.
Weight gain
Hyperprolactinaemia
Sedation
EPSE
Hyperlipidaemia
Postural hypotension
Other cardiovascular effects
Hyperglycaemia This Medicines Management tool is intended to be used assist clinicians and practitioners with the making of prescribing decisions, to target prescribing to produce a care plan that fits the individuals’ holistic needs. The tool is a summary of current evidence for the selection of antipsychotics. Suggested monitoring parameters are included, as well as strategies for the prevention and management of side effects. There are a range of baseline and yearly monitoring parameters which vary dependent on which medications are being taken.
Any tests and monitoring are the responsibility of the prescriber. The presence of adverse effects of medication should be considered on each occasion that an individual is reviewed.
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Weight Gain
Risk/extent of weight gain
Low
Asenapine, Pimozide
Mild
Amisulpride, aripiprazole, fluphenazine, haloperidol,
sulpiride, trifluoperazine,
Moderate
Chlorpromazine, flupentixol, paliperidone, pipotiazine, quetiapine, risperidone, zuclopenthixol
High
Clozapine, olanzapine
Background
People with schizophrenia are at increased risk of weight gain. There is no evidence that
antipsychotics have any direct metabolic effect but many antipsychotics increase appetite
although some of the newer agents to a lesser degree.
Predisposing factors include:
Monitoring of Weight
Baseline waist circumference, weight and measurement of BMI
An on line calculator is also available
o http://www.nhs.uk/Tools/Pages/Healthyweightcalculator.aspx
Ranges of body mass index : weight(Kg)/height²(m²)
<17 - moderate to severe chronic protein-energy malnutrition (severe if <15)
17-20 - chronic protein energy malnutrition but some normal subjects
20-25 - desirable (some authorities 19-25)
25-30 - mildly overweight (grade I obesity)
30-40 - grade II obesity
>40 - grade III obesity
Younger age
Lower BMI
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Cardiovascular risk is increased if waist circumference exceeds following values
Men- 94cm (37 inches)
Women- 80cm (31.5 inches)
Asian Men- 90cm (35 inches)
Asian women- 80cm (31.5 inches)
Cardiovascular risks are increased if BMI is over 25 (ideal BMI = 20 to 24.9)Measure
waist circumference, weigh and calculate BMI monthly for the first 6 months
Weekly monitoring of weight is recommended early in treatment
Monitor waist circumference, weight and BMI every 3 months after first 6 months
GPs and other primary healthcare professionals should monitor at least once a year
Consider need for more frequent monitoring if increased weight is identified
Strategies for Minimisation of Weight Gain
Choose low association agent whenever possible
Prior to commencement discuss expected benefits and drawbacks of medication
Discuss information regarding the potential for weight gain
Encourage low fat, high fibre diet rich in fruit, vegetables and complex carbohydrates
Educate on link between sugary drinks and weight gain
Encourage exercise that builds on the individuals usual activities
Promote good sleep patterns
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Management of Weight Gain
Assess for possible causes of increased weight
Recent smoking cessation
Pregnancy
Follow Trust Guidelines
for the Prescribing
of Medication
in Pregnancy
Physical Considerations
Thyroid function
FBC
LFTs
Albumin
Electrolytes
Stabilise physical parameters
Medication Review
Consider contribution of antipsychotic
Consider role of other medication
Consider switch to antipsychotic with lower association with weight
gain
Follow Guidelines for Antipsychotic Medication Switches
Assess mental state regularly e.g. BPRS
Increased monitoring
Consider referral to Primary Care for weight management
Dietary advice
Lifestyle changes
Cognitive techniques
Consider referral to Primary Care for weight management
Dietary advice
Lifestyle changes
Group
Cognitive techniques
Increased monitoring
Abnormality detected
Weight gain unresolved
Switch
Dietary advice not sufficient or decision not to switch
Normal
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Hyperprolactinaemia
Incidence/severity of hyperprolactinaemia
Very low
Aripiprazole, clozapine
Low
Asenapine, olanzapine, quetiapine
Moderate
Amisulpride, flupentixol, paliperidone,
risperidone, sulpiride, zuclopenthixol
High
Chlorpromazine, fluphenazine, haloperidol,
pimozide, pipotiazine, trifluoperazine,
Background
While there is no consistent correlation between antipsychotic dose, prolactin concentration and the occurrence of symptoms, elevated prolactin levels can be manifested by the following symptoms:
Sexual dysfunction- such as reduced libido, impotence and anorgasmia
Amenorrhea
Galactorrhoea- breast milk production in the male or female
Osteoporosis
Infertility
Gynaecomastia Prolactin elevating drugs (Amisulpride, sulpiride, risperidone FGAs) should ideally be avoided in patients under 25 yrs (ie before peak bone mass), patients with osteoporosis and patients with a history of hormone-dependent breast cancer.
Monitoring for the Effects of Raised Prolactin
Consider baseline prolactin - especially when using agents known to elevate prolactin
Check against current reference values
Complete sexual history and details of menstrual difficulties when appropriate
Use a recognised, evidence based tool for screening of sexual side effects-SESCAM
Reassess when symptoms suggestive of hyperprolactinaemia present
Strategies for Minimisation of Hyperprolactinaemia
Choose low association agent whenever possible
Prior to commencement discuss expected benefits and drawbacks of medication
Discuss information regarding the potential for side effects associated with hyperprolactinaemia
Addition of Aripiprazole to existing treatment in symptomatic patients
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Management of Hyperprolactinaemia
Assess possible causes of symptoms associated with hyperprolactinaemia
Prolactin level check-compare to baseline where one is available
Antipsychotic dose reduction OR
Switch to lower association agent
Monitor mental state – BPRS
Inform female individuals of potential return of menstruation and offer support and contraceptive advice
Review symptoms of hyperprolactinaemia at regular intervals
Resolution of symptoms of
hyperprolactinaemia
Investigate possible physical causes of hyperprolactinaemia E.g. prolactin secreting tumour
Symptoms of hyperprolactinaemia
persist
Recheck prolactin
Physical cause identified No
Yes- and corrected
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Sedation
Background
Sedation can be separated into non- specific sedation, which is characterised by drowsiness and somnolence and specific sedation, which is characterised by psychomotor inhibition and psychic indifference. While the sedative properties of medication can be perceived useful for individuals who are very agitated or aggressive, they can adversely affect well being and functional capability.
Negative aspects of the illness such as apathy should be differentiated from sedation.
Consider the potential for depression.
Sedation is more prominent during the early stages of treatment.
Some degree of tolerance may develop.
Degree of sedation can be such that the individual becomes unaware of the level of sedation that they are experiencing and perceive it normal.
Monitoring for the Effects of Sedation
Consider a detailed assessment of the individuals current sleep pattern and history, especially if using atypical associated with high levels of sedation.
Utilise sleep charts to identify problems.
Assessment by the bed partner can provide additional information about the individual’s behaviour whilst asleep, when appropriate.
Strategies for Minimisation of Sedation
Inform individuals of the risks that medication may cause sedation and advise against driving or using machinery if affected.
Advise that sedation is sometimes more common in the early stages of treatment.
Emphasise the need to review, should they experience sedation.
Incidence/severity of sedation
Very low
Amisulpride, aripiprazole, sulpiride, sertindole
Low
Asenapine, flupentixol, fluphenazine, haloperidol, paliperidone pimozide, risperidone, trifluoperazine,
Medium
Olanzapine, pipotiazine, quetiapine, zuclopenthixol,
High
Chlorpromazine.
Very high
Clozapine
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Management of Sedation
Individual reports sedation
Assess risks of medication
Symptoms
suggestive of negative features of schizophrenia
suggestive of depression
Consider
Taking once daily doses at bedtime?
Asymmetrically splitting dose of twice daily doses, with majority of dose at bedtime
Change to low association agent
Allow 3 to 4 weeks on medication to allow for tolerance
Sedation resolved or does not impede on functional capability
Sedation unresolved
Review antipsychotic dose and/or assess need for
antidepressant
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Extrapyramidal Side Effects (EPSE)
Incidence/severity of EPSE
Very low
Aripiprazole, clozapine, olanzapine, quetiapine, sertindole
Low
Amisulpride, asenapine, paliperidone, risperidone (low dose), sulpiride ,
Medium
Chlorpromazine, flupentixol, pimozide, pipotiazine, risperidone (above low dose), trifluoperazine
High
Fluphenazine, haloperidol, zuclopenthixol
Background
EPSE can be divided into four types:
Dystonias- usually acute and within a few days of treatment
Parkinsonian-usually appear in first few months of treatment
Akathisia- can occur in first few weeks of treatment
Tardive Dyskinesia- late onset, may be irreversible There is evidence that certain groups are more susceptible to EPSE, even with the atypical antipsychotics. These include:
First episode
The elderly (especially females)
Presence of affective symptoms
Younger individuals- acute dystonia
Males- acute dystonia The risk of EPSE with all the atypical agents is much lower than with the conventional antipsychotics, but there is still the potential for individuals to experience a difficult side effect that society has little or no understanding of. The occurrence of EPSE plays a significant role in non-concordance.
Monitoring for EPSE
Careful monitoring is essential, especially with mild to moderate EPSE. The individual should be assessed prior to treatment using a validated assessment tool such as: Side Effects Scale/Checklist for Antipsychotic Medication (SESCAM- Bennett 1995)
2 part scale- observer and self rated
First part focused on EPSE
Second part focused on other known side effects
Includes description of assessment procedure, severity ratings and glossary Modified Abnormal Involuntary Movement Scale (AIMS- Munetz & Benjamin 1988)
12 item scale
Assesses presence and severity of Tardive Dyskinesia
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Dependent mainly on examination and observer ratings
Includes instruction for examination procedure Monitoring should be carried at baseline and then biannually if asymptomatic. Should symptoms emerge the increased frequency of monitoring is established by the effectiveness of remedial strategies.
Strategies for Minimisation of EPSE
Use lowest effective dose possible
Use antipsychotic monotherapy wherever possible
Re-assess need for antipsychotic regularly
Consider withdrawing other drugs that may induce/exacerbate movement disorders
Drug Treatment of EPSE
The evidence for the effectiveness of drug treatment is more robust for the treatment of dystonia and parkinsonian type symptoms. The treatment of akathisia and tardive dyskinesia is largely based on small case reports.
Dystonia Oral, intramuscular (IM) or intravenous (IV) anticholinergic medication depending on severity of symptoms
Individual may be unable to swallow
Response to IV usually within 5minutes
Response to IM usually around 20minutes
Response to oral medication may take up to 2 hours Parkinsonian type
Oral anticholinergic medication
Do not prescribe at night (symptoms usually absent during sleep)
Majority of individuals do not require long term treatment
Review continued need at least 3 monthly
May induce dependence
May induce psychosis
Have a range of adverse side effects
Potentially lethal in overdose Akathisia
Anticholinergics are generally unhelpful All treatments are unlicensed-
Propranolol 30 to 80 mg daily
5-HT2 antagonists such as mirtazapine, trazodone, mianserin
Cyproheptadine 8 to 16mg daily
Clonazepam 500micrograms to 3mg daily Tardive dyskinesia
Anticholinergics may exacerbate
Tetrabenazine started at 12.5mg daily and titrated to 25 to 200mg daily is the only licensed treatment
Benzodiazepine use, intermittent use preferable to avoid tolerance
Propranolol 40-120mg daily Vitamin E 400-1600IU/day
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Management of EPSE
Individual presents with symptoms suggesting EPSE
Assess using validated instrument
SESCAM
AIMS
Consider switch to agent with lower association with
EPSE
Consider relative risk of prescribed medication
Antipsychotic
Other medication
Monitor mental state
Strategies to minimise EPSE
lowest effective dose possible
monotherapy wherever possible
assess need for continued antipsychotic
withdraw other medication that may exacerbate EPSE
Consider drug treatment of
EPSE
Medication has associated risks
No associated risks
YES
NO
Resolution of symptoms or reduction to acceptable level
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Hyperlipidaemia There are no large scale trials that quantify the effects of atypical antipsychotics on lipid metabolism. Several studies suggest that changes in lipid profile are concordant with weight changes and that clozapine and olanzapine tend to be associated with adverse changes in serum concentrations of triglyceride and cholesterol. This is reflected in the SPC for olanzapine therapy, reporting elevated serum cholesterol levels as common and elevated triglyceride levels as very common. Additionally changes from levels of total cholesterol (serum fasting levels) within desirable range at baseline to high levels post therapy were noted as common The SPC for clozapine notes very rare hypercholesterolemia and for quetiapine the SPC notes evidence of adverse lipid profile in clinical studies. There are reports of hyperlipidaemia with phenothiazine therapy and included in the SPC for zuclopenthixol.
Background
Antipsychotic induced weight gain is known to be associated with hyperlipidaemia. Under standard 4 of the National Service Framework for Coronary Heart Disease (CHD), the role of the GP and primary health care team to identify individuals who are at risk of CHD, but who are asymptomatic has been highlighted NICE CG 67 – Lipid Modification –Cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease was re-issued in March 10. Blood cholesterol has a log-linear relationship to the risk of CHD and is a key modifiable factor .Blood cholesterol can be reduced by dietary change, physical activity and medication. Treatment should be aimed at reducing overall CHD risk .A combined approach that addresses all risk factors yields most benefit. Elevated serum cholesterol is considered an independent risk factor for the development of CHD and a fasting lipid profile is recommended every 5 years for all individuals of 20 years and above, regardless of cardiovascular risk status.
Monitoring for Hyperlipidaemia
Check fasting serum cholesterol prior to treatment
Assessment should include Thyroid Stimulating Hormone (TSH) if dyslipidaemia is present
Reassess fasting serum cholesterol 3 months after initiation of treatment
Monitor as appropriate, depending on results and other risk factors
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Classification of serum cholesterol levels
Serum Lipid Concentration mmol/L Classification
Low density lipoprotein- LDL
< 2.59 Optimal
2.59 to 3.34 Near or above optimal
3.36 to 4.11 Borderline high
4.14 to 4.89 High
≥ 4.91 Very high
Total cholesterol- TC
< 4.0 Desirable
≥ 4.0 High
High density lipoprotein- HDL
<1.0 Low
≥ 1.55 High
< = less than, > = more than and ≥ = greater than or equal to
The risk for CHD should be calculated using an appropriate risk calculator (NICE) which in addition to current lipid levels takes account of other positive risk factors:
Older age- 45 years and above in males, 55 years and above in female
Smoking
Obesity
Hypertension- BP of or above 130/80 mmHg
HDL concentration of less than 1.0 mmol/L in men or 1.2mmol/L in women
Family history of premature heart disease
Ethnicity
Abnormal fasting blood glucose levels Diabetes is a risk factor equivalent to CHD
The risk factor is individual to the patient and should be recorded with primary care consultation records. People with the following pre-existing conditions do not require risk assessment as they meet the requirement for secondary treatment:
CHD or angina
Stroke or TIA
Peripheral Vascular Disease Risk equations should not be used for people who are at high risk of CVD due to the following conditions, as they have specific treatment considerations:
familial hypercholesterolemia – treated by specialist management
diabetes – treated under NICE management of type 2 diabetes (update) CG 66.
People older than 40 should have their estimate of cardiovascular (CVD) risk reviewed on an ongoing basis. Offer the patient information about the absolute risk of CVD and absolute benefits and harms of an intervention over a 10 year period- see www.npci.org.uk for decision aids. (NICE 2010)
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Strategies for Minimisation of Hyperlipidaemia
Use low association agent when possible
Encourage lifestyle changes
Monitor weight regularly and take appropriate action in cases of weight gain
Monitor serum cholesterol at appropriate intervals
Management of Hypercholesterolemia
. Lifestyle changes appropriate for the improvement of lipid profile include:
Increase physical activity , consider exercise referral systems
Weight reduction
Decreased dietary intake of saturated fat and cholesterol
A cardioprotective diet (Including 5 portions of fruit and vegetables a day and 2 portions of oily fish a week as per NICE )
If lifestyle changes are insufficient then additional measures should be taken for an additional six weeks:
Reinforcement of lifestyle changes
Referral to a dietician
Consider plant sterols and stanols (note NICE does not recommend routine use of these agents for primary prevention of CVD).
Before offering lipid modification therapy (statins) for primary prevention of CHD all other modifiable CVD factors should be considered and their management optimised if possible (NICE Lipid Modification 2010)
Control BP: The NSF BP target of 140/85 mmHg to reduce risk is challenging, in practice it may not be possible to achieve this for every patient within high risk groups , hence audit criteria of 150/90 mmHg ( also adopted by General Medical Service -GMS Quality and Outcomes Framework as a target for the CHD clinical domain )
Smoking Cessation: Offer advice about how to stop smoking including advice on nicotine replacement therapy.
Advice on other modifiable risk factors and personalised advice about how they can be reduced, including advice about physical activity, diet, alcohol consumption, weight and diabetes should be provided.
Should measures prove insufficient to reduce lipids and CHD risk then a change to a lower association atypical if possible, mental state should be monitored accordingly. If a change to a lower association agent is not possible pharmacological treatment for hypercholesterolemia may be necessary.
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Pharmacological intervention Statin therapy is recommended by NICE as part of the management strategy for primary prevention of CVD for adults who have a 20 % or greater 10 year risk of developing CVD (equating to a 15 % or greater CHD 10 year risk) regardless of lipid level. For secondary prevention (existing CVD/CHD) lipid modification therapy should be offered and not delayed by management of modifiable risk factors. Treatment for both primary and secondary CVD should be initiated with simvastatin 40 mg , if there are potential drug interactions or simvastatin 40 mg is contra-indicated a low dose or alternative preparation such as pravastatin may be chosen. In secondary prevention consider increasing statin potency if a total cholesterol of less than 4mmol/L and an LDL cholesterol of less than 2 mmol/L is not attained, taking into account patient preference, co-morbidities, multiple drug therapies and benefits and risks of treatment. Allow 3 months after commencement of statin therapy and each potency increase before repeating lipid levels to assess benefit of treatment. Current GMS QOF contains a target of total serum cholesterol less than or equal to 5 mmol/L within the CHD clinical domain remaining unchanged Within primary prevention NICE does not suggest a target to attain but ongoing monitoring of cholesterol levels (annual) may promote adherence to lifestyle interventions and statin therapy .
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Postural Hypotension
Incidence/severity of hypotension
Very low
Amisulpride, aripiprazole, asenapine, sulpiride,
Low
Flupentixol, fluphenazine, haloperidol, olanzapine, trifluoperazine zuclopenthixol,
Moderate
Paliperidone, pipotiazine, pimozide, quetiapine, risperidone, sertindole
High
Chlorpromazine, clozapine
Background
Postural hypotension is associated with antipsychotics that block alpha1 adrenoreceptors. It is likely to be more problematic in the following groups:
Older individuals
Individuals with cardiovascular disease
Individuals on antihypertensive medication Individuals exhibit varying degrees of tolerance to falls in blood pressure. A drop in systolic pressure in the region of 20 to 30mmHg within 3 minutes of standing, with associated symptoms is adequate for the diagnosis of postural hypotension. Symptoms associated with postural hypotension include:
Feeling faint or fainting Headache
Neck pain Seizures- usually clonic jerks
Weakness or buckling of the legs Angina- particularly after food
Cognitive slowing Light headedness
Monitoring for Postural Hypotension
Morning sitting and standing blood pressure after initiation and dose increments
More frequent monitoring if symptomatic of postural hypotension
Strategies for the Minimisation of Postural Hypotension
Choose agents with lower propensity for causing postural hypotension where possible
Use standardised titrations for dose increments
Consider more cautious titration in higher risk individuals and those who experience symptoms suggestive of postural hypotension
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Management of Postural Hypotension
Individual presents with symptoms suggestive of postural hypotension
Educate individual to minimise postural hypotension
Plan activity before meals
Consume largest meal at night
Decrease alcohol intake
Eat low carbohydrate foods
Avoid large meals
Drinking water may improve symptoms
Avoid prolonged recumbency
Avoid prolonged exercise
Care during hot weather
Keep shower or bath temperature moderate
Raise head of bed 5 to 20o
Resolution of symptoms
Symptoms continue
Switch to lower association agent and monitor mental state
Further education
Other Cardiovascular Side Effects
Stroke
In elderly patients with dementia, antipsychotic drugs are associated with a small increased risk of mortality and an increased risk of stroke or transient ischemic attack. All older individuals should be assessed for risk factors for cerebrovascular events (e.g. hypertension, atrial fibrillation), prior to commencement of any antipsychotic drug.
It is recommended that:
Antipsychotic drugs should not be used in elderly patients to treat mild to moderate psychotic symptoms.
Initial doses of antipsychotic drugs in elderly patients should be reduced (to half the adult dose or less), taking into account factors such as the patient’s weight, co-morbidity, and concomitant medication.
Treatment should be reviewed regularly Risperidone holds a licence for the short-term treatment (up to 6 weeks) of persistent
aggression in patients with moderate to severe Alzheimer’s dementia unresponsive to non-pharmacological interventions and when there is a risk of harm to self or others.
There is very limited evidence for the efficacy of atypical or typical antipsychotic drugs for the treatment of symptoms of psychosis in dementia.
A clinically significant degree of improvement has only been demonstrated for aripiprazole, with NNT of 13.8
QTc Prolongation
Zotepine may cause significant prolongation of the QTC interval. The use of zotepine should be avoided in individuals with a history of:
Coronary heart disease
Cardiac failure
Arrhythmia
Myocarditis and Cardiomyopathy
Potentially fatal myocarditis (usually occurring in the first 2 months of treatment) and cardiomyopathy (occurring at anytime) are rare serious effects of clozapine. Individuals who have a history suggestive of heart disease should be assessed by a specialist before commencing treatment with clozapine.
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Hyperglycaemia
Incidence of hyperglycaemia/risk of developing /exacerbating diabetes mellitus
Minimal Amisulpride , aripiprazole, asenapine
Low Asenapine, high potency first generation antipsychotics eg haloperidol, pimozide,
Moderate Quetiapine, risperidone, phenothiazines
High Clozapine olanzapine
Background
The prevalence of diabetes mellitus among individuals with schizophrenia is around twice that in the general population. Traditional and atypical antipsychotics may further increase the risk of developing diabetes. Much of the information about the risk of hyperglycaemia is based on retrospective analyses of large databases. The difficulty in adjusting for confounding factors and there is a clear need for more robust evidence to assess the relative risks of individual antipsychotics. Most, but not all, analyses have suggested an increased risk with atypical antipsychotics as a group. Known risk factors for hyperglycaemia include:
Age of 45 or more
Positive family history
Pre-existing obesity - ≥ 20% above desired body weight or BMI ≥ 25
Physical inactivity
Ethnic factors- African, Asian, Afro-Caribbean origin
Impaired glucose tolerance- fasting plasma glucose of ≥ 5.55mmol/L but < 6.99mmol/L
Hypertension- BP ≥ 140/90mmHg
HDL cholesterol less than 0.9 and or triglycerides more than 2.82mmol/L
History of gestational diabetes or delivery of baby weighing > 4kg
Polycystic ovary syndrome or history of vascular disease It is suggested that the risk of developing diabetes during therapy is cumulative and not associated with initial therapy alone.
Monitoring for Hyperglycaemia
Baseline random or fasting plasma glucose prior to initiation
Serum glucose concentration 3 to 4 monthly for first year to check for hyperglycaemia- glucose concentration ≥ 8.9mmol/L but < 11.0mmol/L
Subsequently for high risk individuals- check serum glucose concentration 6 monthly
Individuals with no additional risk factors- check serum glucose concentration 12 monthly
Strategies for the Minimisation of Hyperglycaemia
Use low association agent where ever possible
Advise individuals on prophylactic lifestyle changes when prescribing an atypical antipsychotic particularly those associated with weight gain or hyperglycaemia
Advise individual to report first signs of polyuria (excess urination) and polydipsia (excess drinking)
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Management of Hyperglycaemia
Switch to atypical with lower association with
hyperglycaemia
Monitoring indicates signs of hyperglycaemia
Encourage lifestyle changes
Levels maintained within normal limits
Monitor mental state
Already on low association agent or switch would
adversely affect mental state
Consider use of oral hypoglycaemic agent
YES
NO
EFFECTIVE
INEFFECTIVE
EFFECTIVE
Monitoring Parameters for Antipsychotics
Patient Name: Date of Birth: NHS Number:
Agent Prescribed:
Date:
Height (m) Date:
Amisulpride Aripiprazole Clozapine Olanzapine Quetiapine Risperidone Zotepine Typical Agents
Baseline Repeat (min annually)
N = NORMAL A = Abnormal
Weight Y Y Y Y Y Y Y Y
Waist Y Y Y Y Y Y Y Y
BMI Y Y Y Y Y Y Y Y
BP Y Y *SM Y Y Y Y Y
Blood lipids Y Y Y Y Y Y Y Y
ECG Y Y Y Y Y Y Y Y
FBC Y Y *SM Y Y Y Y Y
FPG/ HbA1c Y Y Y Y Y Y Y Y
Prolactin Y N N Y N Y Y Y
LFTs N B Y Y B B B B
TFTs Y B B B B B B B
U&Es B B B B B B B B
*SM = specific monitoring is required under the terms of the SPC N = no requirement for monitoring this parameter
B = best practice Y = monitoring required